An in Vitro Model to study Inhibition of axon regeneration mediated by anti-glycan antibodies

ROZÉS SALVADOR, VICTORIA; PALANDRI, ANABELA; EDUARDO GARBARINO-PICO; PABLO HECTOR HORACIO LOPEZ

Mendoza

Congreso; 48th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2012

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Axon regeneration is a response of injured nerve cells that is critical for the restoration of structure and function after PNS or CNS injuries; this response is key to recover from neurological disorders like acute immune neuropathy called Guillain Barré Syndrome (GBS). Some studies associate the presence of anti- ganglioside antibodies (anti-Gg abs) with poor recovery in GBS. Patients with incomplete recovery have impaired nerve repair. It was recently demonstrated in a passive transfer animal model that anti-Gg abs can halt axon regeneration. Defining the signaling pathways that prevent regeneration of injured axons can provide key insights to allow development of therapeutic approaches to enhance axon growth. For this, we developed an in vitro model of axon regeneration using dorsal root ganglion (DRG) explants with peripheral nerve. We observed axon inhibition of DRG neurons by treating cultures with an anti-Gg mAb (GD1a/GT1b) associated with the presence of end-bulb like structures characteristic of dystrophic growth cones. Also, cultures were infected with VSV-G-pseudotyped lentivirus vector carrying the GFP sequence taking advantage of its greater trofism for neurons to keep track of regenerating axons on nerves. This approach gave us a useful tool to characterize anti-Gg Ab-induced dystrophic growth cones and will help to clarify the pathogenic role of anti-Gg abs in GBS